Headache is the most common pain-related complaint and the seventh leading ailment seen in medical practice, accounting for 18 million physician visits each year 1. Recent evidence from a variety of sources indicates that inflammation of the dura is important for recurrent headache disorders. Chronic daily headache (CDH) is a pain disorder characterized by >15 headache days per month and affects up to 4% of the general population. Most cases of CDH evolve from episodic migraine. Little is known about how episodic migraine transforms into CDH, in part, because there are currently are no validated animal models to study the pathophysiology of CDH. In the preliminary data for this application, we report the development of a model of CDH using repeated application of inflammatory soup to the dura in awake, behaving rats. These data indicate that repetitive stimulation of the dura with an inflammatory soup (IS) leads to chronic pressure and brush allodynia in the periorbital region of the rat. Following the first few infusions of IS, changes in sensory thresholds resolve in hours. After multiple infusions, there is a chronic allodynic state that persists. In addition, in many of the rats, allodynia spreads to extracephalic regions of the body. Based on our preliminary findings, we propose the following 2 specific aims to test the hypothesis that repetitive infusion of IS on the dura is an accurate model for studying the pathophysiology of chronic daily headache. These aims will demonstrate that this system models CDH because it responds to proven clinical treatments of CDH in humans. Aim 1 will test the hypothesis that established preventive treatments for migraine in humans will block the transition of the rats from episodic to chronic trigeminal pain following repetitive IS infusion on the dura. Aim 2 will test the hypothesis that acute migraine treatments such as triptans are less effective in rats that have received chronic IS infusions. [unreadable] [unreadable] [unreadable]